Biofilm Control Activity of Triphenylphosphonium-Conjugated Curcumin Against Staphylococcus aureus

Hospital- and community-acquired Staphylococcus aureus infections are dominated by their biofilms and cause difficult-to-treat persistent infections. As an alternative anti-biofilm agent, the efficacy of triphenylphosphonium (TPP)-conjugated curcumin (TPP-curcumin) was determined against S. aureus biofilms in comparison to that of curcumin and commercial antibiotics. TPP-curcumin elicited strong anti-staphylococcal activity with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 3.125 and 6.25 μM, respectively. The MIC and MBC values for curcumin and ampicillin were > 125 and > 286.2 μM (100 μg/mL), respectively. The MIC and MBC values were 25.7 μM (12.5 μg/mL) and 103 μM (50 μg/mL), respectively, for kanamycin. TPP-curcumin was multi-fold more effective than curcumin in inhibiting biofilm growth. Minimum biofilm inhibitory concentration (MBIC) values of TPP-curcumin, curcumin, ampicillin and kanamycin were 3.125, > 125, > 286 and 25 μM, respectively. Besides inhibiting biofilm formation, TPP-curcumin has effectively killed S. aureus cells in pre-formed or established biofilms. Treatment of biofilms with 25 μM TPP-curcumin achieved near-complete cell killing. Exposure to TPP-curcumin led to severe membrane damage and oxidative stress in S. aureus cells. The strong antimicrobial and antibiofilm activity of TPP-curcumin suggests its potential use for developing or augmenting antibacterial therapies for drug-resistant S. aureus infections.